The goal of the current proposal is to better understand the complex multifactorial etiology of developmental dyslexia, or reading disability (RD), by focusing on gene x environment interactions. RD is defined by deficits in fluent word recognition that are accompanied by poor spelling and decoding abilities, all of which typically stem from underlying weaknesses in the phonological component of language. RD is often referred to as a communication disorder, especially in school settings, because it causes impairments in written language communication. The genetics of RD has advanced to the point of identifying candidate genes, but the identification of these genes is unlikely to answer many of the etiological questions about RD, unless interactions with the environment are considered. As such, this proposal will test for gene x environment interactions using molecular genetic methods and measures of the home environment and the prenatal and perinatal environment. Because only limited information about the home environment was obtained at the time of testing, follow-up questionnaires targeting the home literacy environment and family educational values will be mailed to the families. The study is a sib-pair linkage design that will utilize genotypes and phenotypes from dizygotic twins and their biological siblings who were previously recruited into a large twin study. The genotypes will target markers in 6 of the replicated linkage regions for RD: 1p36-p34, 2p16-p15, 3p12-q13, 6p22.2, 15q21,and 18p11.2. Composite phenotypes assessing word recognition, phonological decoding, phonological awareness, verbal working memory, orthographic coding, and rapid naming will be constructed. Linkage peaks in each of the 6 genomic regions of interest will be identified using these composite phenotypes. Then, additive and interactive models of genetic and environmental contributions to the phenotypes will be tested at these linkage peaks. The analyses will implement extensions of regression-based linkage methods in order to test for gene x environment interactions. This project has relevance for public health because RD has implications for academic and occupational success and it is associated with decreases in self-esteem, motivation, and social-emotional functioning. Although there are empirically-validated treatments available, many children are not diagnosed until they have already fallen behind in reading. Thus, studies to better understand the complex genetic and environmental causes of RD could facilitate early identification and intervention enabling better academic, psychological, and occupational outcomes. [unreadable] [unreadable] [unreadable]